The overall aim of this project is to analyze the immune response to Toxoplasma gondi in order to define which cellular immune components and parasite target antigens are involved in the control of infection and its breakdown in immunocompromised hosts. Progress was made this year in the following areas: A. Analysis of Class I MHC presentation pathways and CD8+ cell target molecules utilized by T. gondii. Bone marrow macrophages were shown to process soluble T. gondii antigens for presentation to CD8+ T cells by an endogenous pathway. A preliminary analysis of the processed parasite proteins and CTL target peptide epitopes was performed. B. Role of cytokines in down-regulation of macrophage-mediated killing of T. gondii and T. cruzi. IL-10, IL-4 and TGF-~ were shown to down-regulate the intracellular killing of T. gondii by activated macrophage through the inhibition of nitrogen oxide production. Parallel results were found with a related intracellular parasite, Trypanosoma cruzi. C. Role of NK cells in the cytokine response to T. gondii. T. gondii was shown to trigger the T lymphocyte-independent production of IFN-gamma by NK cells. SCID mice depleted of NK cells were shown to be more susceptible to infection, and NK cells were shown to replace CD8+ cells as the primary effectors of immunity in vaccinated beta2-microglobulin- deficient mice.